Bone marrow transplantation has the potential of providing a complete cure of the disease symptoms of hemoglobinopathies. Successful application of mismatched (related-haploidentical) bone marrow transplantation to patients with sickle cell disease or a thalassemia requires that allochimerism be achieved and stabilized in the bone marrow with less morbidity and mortality than are being experienced in existing mismatched bone marrow transplantation (BMT) protocols. This goal requires use of less total body radiation and less drug myeloablation in support of the transplantation. Mixed chimeric bone marrow states have been achieved and stabilized in mice through the use of psoralen photochemically treated donor leukocytes which are blocked in their proliferative capabilities but which retain their immunological activities. Model mouse bone marrow transplantation experiments, in a complete MHC mismatch setting, have recently demonstrated that under low dose myeloablative radiation conditions and in the absence of myeloablative and immunosuppressive drugs, S-59 (a psoralen) photochemically treated (S-59 PCT) T-cell add-backs promote and stabilize allochimerism with greatly reduced risk of graft versus host disease (GVHD). With the completion of this validation through the support of US Public Health Service Grant R01 HL63456 "Stem Cell Transplantation to Establish AIIochimerism," this project is now entering a development phase that should ultimately lead to an approved clinical protocol of pediatric allogeneic stem cell transplantation. This success has resulted from a very productive collaboration between Children's Hospital Oakland Research Institute and Cerus Corporation. This collaborative team has now concluded that the best approach for access to a clinical test in pediatric patients for sickle cell disease or for thalassemia requires a validation in the dog model for transplantation at the Fred Hutchinson Medical Center in Seattle. The dog experiments will be initiated in Phase II of this SBIR. Phase I will be the in vitro validation of the S-59 photochemical treatment of dog leukocytes using the Cerus cell proliferation assay, the induced cytokine synthesis assay, and the induced surface antigen expression assay. The specific aim of Phase I will be met when the photochemical conditions have been found that are required to reduce the dog T-cell proliferation to 95 percent of untreated dog T-cells. These cells must have retained viability.